Hyperlipidemia Flashcards
Pathophysiology of Hyperlipidemia
Atherosclerosis major cause of CAD
Lipoproteins: all contain triglycerides, phospholipids, & cholesterol
- Low-density lipoprotein (LDL)
- High-density lipoprotein (HDL)
- Very-low-density lipoprotein (VLDL)
- Triglycerides
Exogenous pathway: involves absorption of lipids via intestine
Endogenous pathway: lipids originate from liver
Cholesterol Screening
All adults older than 20 years of age
Fasting lipid profile at least every 5 years
Lifestyle modification: balanced diet, weight loss, minimizing risk factors
- Hyperglycemia, smoking, high-fat diet
Childhood screening in those with risk factors: DM, obesity, family hx of familial hypercholesterolemia
- Emphasis on diet & exercise
Lifestyle Modifications for Hyperlipidemia
Exercising 30 minutes/day
Dietary Therapy
- Reduced intake saturated fats not as strong
- Consuming plant sterols (2 g/day)
- Increased soluble fiber intake (10-25 g/day)
- Dietary fiber of 20-30 g/day
- Total calories to maintain or lose weight
Drug Therapies for Dyslipidemia
HMG-CoA (3-hydroxy-3-methy-glutaryl-coenzyme A) reductase inhibitors
- Lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin
Fibrates: Fibric acid derivatives
- Gemfibrozil, micronized fenofibrate, clofibrate
Bile Acid Sequestrants
- Cholestyramine, colestipol, colesevelam
Ezetimibe (Zetia): most effective in combination with statin
Vitamins and Supplements for Hyperlipidemia
Vitamins/antioxidants/herbs/natural products
- coenzyme Q10 is gaining evidence as good to take with statin
- Niacin (Vitamin B3) no longer FDA approved for treatment
Rational Drug Selection for Hyperlipidemia
Lifestyle changes & no medication therapy for those with CV risk less than 7%
If cardiac risk fi greater than 7%, statin recommended
- Degree & number of risks determine if statins should be pushed aggressively or started at more moderate levels
Active liver disease is a contraindication for all anti-lipidemics except the bile acid sequestrants
Statins- HMG-CoA Reductase Inhibitors: Pharmacodynamics
- Block synthesis of cholesterol in liver by competitively inhibiting HMG-CoA reductase activity
- Decrease levels of LDL by 25-65%
- Modest decreases in TG (10-40%) & very modest increases in HDL (5-17%) may occur with more potent statins
- Pregnancy: contraindicated (old category X)
Fibrates- Fibric Acid Derivatives: MOA & Effects on lipids
MOA:
- inhibition of cholesterol synthesis
- decreased TG synthesis
- inhibition of lipolysis in adipose tissue
- decreased production of VLDL/increased clearance
- increased plasma & hepatic lipoprotein lipase (LPL) activity
Effects on lipids:
- Decreases TC, LDL, & TGs; increases HDL
Bile Acid Sequestrants: Pharmacodynamics
- By promoting an increase in bile acid excretion, they enhance conversion of cholesterol to bile acids by the liver and increase uptake of LDL
- They bind with cholesterol in intestine and are not metabolized by liver
- They are excreted in bound form in feces
- They may be used in patients with active liver disease
- They lower TC, LDL, & TG and increase HDL
Ezetimibe (Zetia): Pharmacodynamics
- Selectively inhibits the intestinal absorption of cholesterol & related phytosterols
- Has been shown to reduce TC, LDL, & TG while increasing HDL-C
- Most effective in combination with statin
- Not for children younger than 10 years
Hyperlipidemia: Vitamins & Complementary, & Alternative Medicine
Vitamin E
- Consumption more than 100 IU/day for more than 2 years lowers rate of CHD progression
- Fat soluble; can accumulate; watch in patients with bleeding problems, ulcerative colitis
Beta carotene: increase physicians’ health study
Vitamin C: increased fibrinolytic activity, decreased platelet adhesiveness, decreased TC
Selenium: antioxidant, limited clinical evidence
- 100 mcg/day for CHD, watch toxicity
Folic acid: reduction in plasma homocysteine levels
Herbs: garlic, fish oils, oat bran, coenzyme Q10
Hyperlipidemia- Children & Adolescents: Pharmacodynamics, Treatment
Genetic disorders of lipid metabolism
TC goal less than 170 mg/dL
Primary prevention best for lifestyle- associated hyperlipidemia
- Diet & exercise
Treatment
- Fiber, plant sterols, & omega-3 fatty acids
- Nicotinic acid
- Statins for familial hypercholesterolemia after puberty
Hyperlipidemia- Patient Variables (middle-aged men, women, older adults, young adults)
Middle-aged men: Statins for high-risk patients; combination of statins & bile acid sequestrants
Women 45-75 years: statins if CHD risk; Hormone replacement therapy (HRT) not recommended for LDL lowering, esp. if combined w/ progestin
Older adults: statins first-line treatment; bile acid sequestrants may cause impaction if on fluid restrictions
Young Adults: maximization of lifestyle changes; pregnancy risk with many drugs
Hyperlipidemia- Patient Variables (African Americans, Asian & Pacific Islanders, DM, Metabolic Syndrome)
African Americans: men- document creatine kinase (CK) before starting statin; treat HTN
Asian & Pacific Islanders: there is higher CHD risk at lower BMI, so early diagnosis is critical
Diabetes Mellitus: increased risk equal to CHD (treated as high risk); statins usually drug of choice; attention to TG as well
Metabolic Syndrome: increased risk of coronary disease; intensive lifestyle changes; statins drug of choice
Hyperlipidemia: Monitoring
- 3 month dietary therapy trial
- Baseline liver function (no frequent checks unless issues), CK, lipid panel
Rechecking of lipid panel at 6-8 weeks & after every dose adjustment
—- Nicotinic acid check in 4-6 weeks - Follow-up at 8-12 week intervals for 1 year after aggressive dosing changes
